Starvation transforms signal encoding in C. elegans thermoresponsive neurons and suppresses heat avoidance via bidirectional glutamatergic and peptidergic signaling

Abstract

. During early food deprivation (1-hr off food), the thermoresponsive sensory neurons AWCs mediate robust heat-evoked reversals over a broad range of stimulus intensities via glutamate and FLP-6 neuropeptide signaling, each covering distinct heat intensity ranges. After six hours of food deprivation (prolonged starvation), heat-evoked reversal responses are nearly abolished, independently of any external food odor cues. Starvation triggers a shift in the distribution of AWC heat-evoked calcium response polarity, transitioning from mostly excitatory responses to a more heterogeneous pattern combining both excitatory and inhibitory activities. This switch relies on ASI neurons, proposed to work as internal state-sensing neurons. INS-32 and NLP-18 neuropeptide signals from ASI switch from a reversal-promoting to a reversal-inhibiting effect. In addition, reversal-promoting glutamatergic transmission by AWC is antagonized by glutamatergic transmission from non-AWC neurons that suppresses FLP-6-dependent reversals. Our findings define a circuit logic by which nociceptive responsiveness gating by internal nutritional state is linked to dynamic modulation of sensory neuron activity patterns and orchestrated by bidirectional glutamatergic and neuropeptidergic signals. More broadly, this study illustrates how sensory systems integrate metabolic information to prioritize behavioral outputs under changing physiological conditions, providing mechanistic insight into the plastic coupling between sensation, internal state, and action selection.

The authors' abstract, as published at the source. eLife, 2026 · DOI ↗